The study is designed to elucidate the mechanism of spontaneous pacemaking in the sinus node. It has recently been proposed that spontaneous depolarization might occur as a consequence of exocytotic discharge of catecholamines from the pacemaking cells, themselves. According to this hypothesis, the discharged catecholamines bind to the outside of the cell membrane and allow calcium entry, which produces depolarization. We plan to test this hypothesis using a number of approaches: (1) A prediction of the hypothesis is that the membrane potential ought to exhibit fluctuations akin to miniature end-plate potentials: the binding of each packet of catecholamines is expected to give rise to a quantal depolarization. We will test whether such a phenomenon occurs in sinus node cells. (2) A corollary of the hypothesis is that the cells within the sinus node are effectively electrically isolated from one another, and that synchronization among pacemaking cells is mediated by stretch. We will test for electrical communication by injecting a tiguous cells; from this we will determine the density of ionic communication channels between sinus node cells, and therefore, the degree of electrical coupling. (3) A fluorescence histochemical approach will be used to localize the catecholamines within sinus node tissue. (4) A mathematical model of the dynamic processes described in the hypothesis will be constructed; this will not only test the reasonableness of the proposed processes, but may provide insight into the mechanism of certain sinus arrhythmias.